(a) Field of the Invention
The invention relates to a novel concept of using microencapsulated genetically engineered microorganisms for clinical application by oral administration.
(b) Description of Prior Art
Recent advancements in molecular biology have furnished a variety of genetically engineered microorganisms with many specialized functions. Unfortunately, it is difficult to use genetically engineered microorganisms for the treatment of patients.
Since parental administration of microorganism into human is too risky and dangerous, even if a very small amount is given.
In accordance with the present invention, this problem was solved by microencapsulating genetically engineered microorganisms and giving them orally. Microencapsulation prevents leakage of microorganism also if a small amount leaks out it is still safe since the gastrointestinal tract can safely contain non-pathogenic microorganism. The present invention describes a model study which can be used for a variety of genetically engineered microorganisms.
More particularly, the present invention demonstrates, as an example, the use of microencapsulated genetically engineered bacteria for the removal of urea and ammonia. Urea and ammonia removal is necessary in cases of kidney failure and liver failure, respectively. Uremia is caused by insufficient kidney function. As kidneys fails, substances normally excreted in the urine are retained in the blood and body tissues. This results in increased concentration of metabolites normally measurable in blood. For example, the blood urea nitrogen (BUN) level increases from 15 mg % to 100-300 mg %, and serum creatinine increases from 1.0 mg % to 10-25 mg %. Similarly, elevated level of ammonia in liver failure is evident. These substances in high concentrations become toxins or poisons and result in severe disturbances of metabolic pathways causing many diseases ranging from organ failure to impaired brain functions. Several attempts, including use of oral feeding of oxystarch and urease zirconium phosphate have been applied to remove these unwanted metabolites from the body fluid compartments without success. The amounts of oxystarch and urease-zirconium-phosphate needed were too large to allow for use in the routine treatment of the patients.
The microencapsulation concept is established to provide specialized environment to the living and non living encapsulated materials (Chang, T. M. S. (1964) Science, 146:524-525). In previous studies, it was shown that microencapsulated genetically engineered bacteria E. coli DH5 has great capacity to remove urea and ammonia from the artificial media and from the plasma in vitro (Prakash, S. and Chang, T. M. S. (1995) Biotechnology and Bioengineering, 46:621-626).
Surprisingly, and in accordance with the present invention, it is demonstrated for the first time that these microencapsulated genetically engineered microorganisms when given orally in very small amounts can effectively remove systemic urea and ammonia in kidney failure rats (Prakash, S. and Chang, T. M. S. (1996) Nature Medicine, 2(8):883-887). This capacity is much higher than any system available to date.